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Downregulation of long non-coding RNA MAFG-AS1 represses tumorigenesis of colorectal cancer cells through the microRNA-149-3p-dependent inhibition of HOXB8

Authors
  • Ruan, Zhiyan1
  • Deng, Hongling1
  • Liang, Minhua1
  • Xu, Zhe1
  • Lai, Manxiang1
  • Ren, Hong1
  • Deng, Xiangliang2
  • Su, Xinguo1
  • 1 Guangdong Food & Drug Vocational College, No. 321, Longdong North Road, Tianhe District, Guangzhou, 510520, P.R. China , Guangzhou (China)
  • 2 Guangdong Pharmaceutical University, No. 280, East Ring Road, Guangzhou University Town, Guangzhou, 510006, P.R. China , Guangzhou (China)
Type
Published Article
Journal
Cancer Cell International
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Oct 19, 2020
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12935-020-01485-4
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundColorectal cancer (CRC) is considered as the second common death-induced cancer. More recently, association of long non-coding RNAs (lncRNAs) with CRC has been extensively investigated. Therefore, the present study was performed to determine whether lncRNA MAF BZIP Transcription Factor G Antisense RNA 1 (MAFG-AS1) could regulate biological activities of CRC cells and unravel the underlying mechanisms.MethodsCRC and corresponding adjacent tissues were collected to determine the expression of lncRNA MAFG-AS1, microRNA-149-3p (miR-149-3p) and homeobox B8 (HOXB8) by RT-qPCR. Dual luciferase reporter gene assay was used to explore the targeting relationship between miR-149-3p and lncRNA MAFG-AS1 and between miR-149-3p and HOXB8, followed by RNA immunoprecipitation for verification. Migration, proliferation, invasion, and apoptosis of HCT116 and LoVo cells were examined when lncRNA MAFG-AS1 was silenced or miR-149-3p was overexpressed. Furthermore, tumorigenicity of HCT116 and LoVo cells was measured in vivo by tumor xenograft in nude mice.ResultsLncRNA MAFG-AS1 and HOXB8 were found to be highly expressed in CRC tissues and cells, while miR-149-3p was under-expressed. LncRNA MAFG-AS1 negatively regulated miR-149-3p while miR-149-3p downregulated HOXB8. In addition, lncRNA MAFG-AS1 silencing by shRNA or miR-149-3p upregulation by mimic suppressed the migration, proliferation, invasion and tumorigenesis but promoted the apoptosis of HCT116 and LoVo cells.ConclusionTaken together, lncRNA MAFG-AS1 downregulation inhibits the malignant behaviors of CRC cells by upregulating miR-149-3p and downregulating HOXB8, providing a potential therapeutic target for CRC treatment.

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